[Effect of PD-L1 blockade on function of dendritic cells derived from chronic myelocytic leukemia].
Programmed death-1 ligand-1(PD-L1) is a recently identified member of the B7 family molecules and is shown to mediate the inhibition of immune responses. This study was purposed to enhance the weak immunological function of dendritic cells (DCs) derived from the patients with chronic myelocytic leukemia (CML) by blockade of the expression of PD-L1. Bone marrow mononuclear cells (BMMNCs) of CML patients were induced into DCs in the presence of cytokine cocktail of rhGM-CSF, rhIL-4 and TNF-alpha. The phenotypes of DCs were detected by flow cytometry, mixed lymphocyte reaction was analyzed by MTT assay and IFN-gamma, IL-2 and IL-10 in the cell culture supernatant were detected by ELISA. The results showed that the expression of PD-L1 on CML-DCs was upregulated with the maturation of CML-DCs. PD-L1-blockaded DCs could enhance T lymphocyte proliferation, increase the secretion of IL-2 and IFN-gamma, and inhibit the production of IL-10. Taken together, PD-L1-blockaded DCs originated from CML cells had more potent immunostimulatory capability. It is concluded that PD-L1 blockaded can enhance the function of CML-DCs. This approach presents new possibilities for achieving anti-tumor immunity by DC-based vaccination.
Wang
Chun-Yan
CY
Department of Hematology and Oncology, The Second Hospital, Lanzhou University, Lanzhou, 730030, Gansu Province, China.
Zhang
Lian-Sheng
LS
Tian
Fa-Qing
FQ
Huang
Rui
R
D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C508609:IL10 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor